tbuckley/cabot-search huggingface dataset:
Air and surface sampling for monkeypox virus in a UK hospital: an observational study
Authors: Susan Gould, Barry Atkinson, Okechukwu Onianwa, Antony Spencer, Jenna Furneaux, James Grieves, Caroline Taylor, Iain Milligan, Allan Bennett, Tom Fletcher, Jake Dunning, Jake Dunning, Nicholas Price, Michael Beadsworth, Matthias Schmid, Marieke Emonts, Anne Tunbridge, David Porter, Jonathan Cohen, Elizabeth Whittaker, Ruchi Sinha
Journal: The Lancet Microbe (2022)
Health-related quality of life in patients given ciltacabtagene autoleucel for relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b–2, open-label study
Authors: Thomas Martin, Yi Lin, Mounzer Agha, Adam D Cohen, Myo Htut, A Keith Stewart, Parameswaran Hari, Jesus G Berdeja, Saad Z Usmani, Tzu-Min Yeh, Yunsi Olyslager, Jenna D Goldberg, Jordan M Schecter, Deepu Madduri, Carolyn C Jackson, William Deraedt, Katharine S Gries, John M Fastenau, Jeremiah J Trudeau, Muhammad Akram, Lida Pacaud, Andrzej Jakubowiak, Sundar Jagannath
Journal: The Lancet Haematology (2022)
Pregnancy outcomes after SARS-CoV-2 infection in periods dominated by delta and omicron variants in Scotland: a population-based cohort study
Authors: Sarah J Stock, Emily Moore, Clara Calvert, Jade Carruthers, Cheryl Denny, Jack Donaghy, Sam Hillman, Lisa E M Hopcroft, Leanne Hopkins, Anna Goulding, Laura Lindsay, Terry McLaughlin, Bob Taylor, Bonnie Auyeung, Srinivasa Vittal Katikireddi, Colin McCowan, Lewis D Ritchie, Igor Rudan, Colin R Simpson, Chris Robertson, Aziz Sheikh, Rachael Wood
Journal: The Lancet Respiratory Medicine (2022)
Effectiveness and durability of BNT162b2 vaccine against hospital and emergency department admissions due to SARS-CoV-2 omicron sub-lineages BA.1 and BA.2 in a large health system in the USA: a test-negative, case-control study
Authors: Sara Y Tartof, Jeff M Slezak, Laura Puzniak, Vennis Hong, Timothy B Frankland, Fagen Xie, Bradley K Ackerson, Srinivas R Valluri, Luis Jodar, John M McLaughlin
Journal: The Lancet Respiratory Medicine (2022)
“Genetic scissors” CRISPR/Cas9 genome editing cutting-edge biocarrier technology for bone and cartilage repair
Authors: Chao Li, Yawei Du, Tongtong Zhang, Haoran Wang, Zhiyong Hou, Yingze Zhang, Wenguo Cui, Wei Chen
Journal: Bioactive Materials (2022)

CRISPR/Cas9 is a revolutionary genome editing technology with the tremendous advantages such as precisely targeting/shearing ability, low cost and convenient operation, becoming an efficient and indispensable tool in biological research. As a disruptive technique, CRISPR/Cas9 genome editing has a great potential to realize a future breakthrough in the clinical bone and cartilage repairing as well. This review highlights the research status of CRISPR/Cas9 system in bone and cartilage repair, illustrates its mechanism for promoting osteogenesis and chondrogenesis, and explores the development tendency of CRISPR/Cas9 in bone and cartilage repair to overcome the current limitations.
Rangeland stewardship envisioned through a planetary lens
Authors: David D. Briske, D. Layne Coppock
Journal: Trends in Ecology & Evolution (2022)

Rangelands comprise approximately 50% of ecologically intact landscapes available to mitigate biodiversity loss and to provide natural climate solutions. However, their planetary value is often overshadowed by local priorities on select provisioning services. A transformative stewardship strategy will require an inversion of priorities placed on ecosystem service categories supplied by rangelands.
Health Misinformation Exposure and Health Disparities: Observations and Opportunities
Authors: Brian G. Southwell, Jessica Otero Machuca, Sabrina T. Cherry, Melissa Burnside, Nadine J. Barrett
Journal: Annual Review of Public Health (2022)

The concepts of health misinformation and health disparities have been prominent in public health literature in recent years, in part because of the threat that each notion poses to public health. How exactly are misinformation proliferation and health disparities related, however? What roles might misinformation play in explaining the health disparities that we have documented in the United States and elsewhere? How might we mitigate the effects of misinformation exposure among people facing relatively poor health outcomes? In this review, we address such questions by first defining health disparities and misinformation as concepts and then considering how misinformation exposure might theoretically affect health decision-making and account for disparate health behavior and health outcomes. We alsoassess the potential for misinformation-focused interventions to address health disparities based on available literature and call for future research to address gaps in our current evidence base.
Orchestration of Collective Migration and Metastasis by Tumor Cell Clusters
Authors: Ami Yamamoto, Andrea E. Doak, Kevin J. Cheung
Journal: Annual Review of Pathology Mechanisms of Disease (2022)

Metastatic dissemination has lethal consequences for cancer patients. Accruing evidence supports the hypothesis that tumor cells can migrate and metastasize as clusters of cells while maintaining contacts with one another. Collective metastasis enables tumor cells to colonize secondary sites more efficiently, resist cell death, and evade the immune system. On the other hand, tumor cell clusters face unique challenges for dissemination particularly during systemic dissemination. Here, we review recent progress toward understanding how tumor cell clusters overcome these disadvantages as well as mechanisms they utilize to gain advantages throughout the metastatic process. We consider useful models for studying collective metastasis and reflect on how the study of collective metastasis suggests new opportunities for eradicating and preventing metastatic disease.
Improving indicator-condition guided testing for HIV in the hospital setting (PROTEST 2·0): A multicenter, interrupted time-series analysis
Authors: Saskia J. Bogers, Maarten F. Schim van der Loeff, Anders Boyd, Udi Davidovich, Marc van der Valk, Kees Brinkman, Kim Sigaloff, Judith Branger, Nejma Bokhizzou, Godelieve J. de Bree, Peter Reiss, Jan E.A.M. van Bergen, Suzanne E. Geerlings
Journal: The Lancet Regional Health - Europe (2022)
Osteoclasts, Master Sculptors of Bone
Authors: Deborah J. Veis, Charles A. O'Brien
Journal: Annual Review of Pathology Mechanisms of Disease (2022)

Osteoclasts are multinucleated cells with the unique ability to resorb bone matrix. Excessive production or activation of osteoclasts leads to skeletal pathologies that affect a significant portion of the population. Although therapies that effectively target osteoclasts have been developed, they are associated with sometimes severe side effects, and a fuller understanding of osteoclast biology may lead to more specific treatments. Along those lines, a rich body of work has defined essential signaling pathways required for osteoclast formation, function, and survival. Nonetheless, recent studies have cast new light on long-held views regarding the origin of these cells during development and homeostasis, their life span, and the cellular sources of factors that drive their production and activity during homeostasis and disease. In this review, we discuss these new findings in the context of existing work and highlight areas of ongoing and future investigation.
Beyond Erectile Dysfunction: cGMP-Specific Phosphodiesterase 5 Inhibitors for Other Clinical Disorders
Authors: Arun Samidurai, Lei Xi, Anindita Das, Rakesh C. Kukreja
Journal: The Annual Review of Pharmacology and Toxicology (2022)

Cyclic guanosine monophosphate (cGMP), an important intracellular second messenger, mediates cellular functional responses in all vital organs. Phosphodiesterase 5 (PDE5) is one of the 11 members of the cyclic nucleotide phosphodiesterase (PDE) family that specifically targets cGMP generated by nitric oxide-driven activation of the soluble guanylyl cyclase. PDE5 inhibitors, including sildenafil and tadalafil, are widely used for the treatment of erectile dysfunction, pulmonary arterial hypertension, and certain urological disorders. Preclinical studies have shown promising effects of PDE5 inhibitors in the treatment of myocardial infarction, cardiac hypertrophy, heart failure, cancer and anticancer-drug-associated cardiotoxicity, diabetes, Duchenne muscular dystrophy, Alzheimer's disease, and other aging-related conditions. Many clinical trials with PDE5 inhibitors have focused on the potential cardiovascular, anticancer, and neurological benefits. In this review, we provide an overview of the current state of knowledge on PDE5 inhibitors and their potential therapeutic indications for various clinical disorders beyond erectile dysfunction.
OAT, OATP, and MRP Drug Transporters and the Remote Sensing and Signaling Theory
Authors: Sanjay K. Nigam, Jeffry C. Granados
Journal: The Annual Review of Pharmacology and Toxicology (2022)

The coordinated movement of organic anions (e.g., drugs, metabolites, signaling molecules, nutrients, antioxidants, gut microbiome products) between tissues and body fluids depends, in large part, on organic anion transporters (OATs) [solute carrier 22 (SLC22)], organic anion transporting polypeptides (OATPs) [solute carrier organic (SLCO)], and multidrug resistance proteins (MRPs) [ATP-binding cassette, subfamily C (ABCC)]. Depending on the range of substrates, transporters in these families can be considered multispecific, oligospecific, or (relatively) monospecific. Systems biology analyses of these transporters in the context of expression patterns reveal they are hubs in networks involved in interorgan and interorganismal communication. The remote sensing and signaling theory explains how the coordinated functions of drug transporters, drug-metabolizing enzymes, and regulatory proteins play a role in optimizing systemic and local levels of important endogenous small molecules. We focus on the role of OATs, OATPs, and MRPs in endogenous metabolism and how their substrates (e.g., bile acids, short chain fatty acids, urate, uremic toxins) mediate interorgan and interorganismal communication and help maintain and restore homeostasis in healthy and disease states.
Toripalimab Plus Chemotherapy for Patients With Treatment-Naive Advanced Non–Small-Cell Lung Cancer: A Multicenter Randomized Phase III Trial (CHOICE-01)
Authors: Zhijie Wang, Lin Wu, Baolan Li, Ying Cheng, Xiaoling Li, Xicheng Wang, Liang Han, Xiaohong Wu, Yun Fan, Yan Yu, Dongqing Lv, Jianhua Shi, Jianjin Huang, Shaozhang Zhou, Baohui Han, Guogui Sun, Qisen Guo, Youxin Ji, Xiaoli Zhu, Sheng Hu, Wei Zhang, Qiming Wang, Yuming Jia, Ziping Wang, Yong Song, Jingxun Wu, Meiqi Shi, Xingya Li, Zhigang Han, Yunpeng Liu, Zhuang Yu, An-Wen Liu, Xiuwen Wang, Caicun Zhou, Diansheng Zhong, Liyun Miao, Zhihong Zhang, Hui Zhao, Jun Yang, Dong Wang, Yingyi Wang, Qiang Li, Xiaodong Zhang, Mei Ji, Zhenzhou Yang, Jiuwei Cui, Beili Gao, Buhai Wang, Hu Liu, Lei Nie, Mei He, Shi Jin, Wei Gu, Yongqian Shu, Tong Zhou, Jian Feng, Xinmei Yang, Cheng Huang, Bo Zhu, Yu Yao, Xiongwen Tang, Jianjun Yu, Ellen Maher, Hui Feng, Sheng Yao, Patricia Keegan, Jie Wang
Journal: Journal of Clinical Oncology (2022)

The CHOICE-01 study investigated the efficacy and safety of toripalimab in combination with chemotherapy as a first-line treatment for advanced non-small-cell lung cancer (NSCLC).Patients (N = 465) with treatment-naive, advanced NSCLC without EGFR/ALK mutations were randomly assigned 2:1 to receive toripalimab 240 mg (n = 309) or placebo (n = 156) once every 3 weeks in combination with chemotherapy for 4-6 cycles, followed by the maintenance of toripalimab or placebo once every 3 weeks plus standard care. Stratification factors included programmed death ligand-1 expression status, histology, and smoking status. The primary end point was progression-free survival (PFS) by investigator per RECIST v1.1. Secondary end points included overall survival and safety.At the final PFS analysis, PFS was significantly longer in the toripalimab arm than in the placebo arm (median PFS, 8.4 v 5.6 months, hazard ratio = 0.49; 95% CI, 0.39 to 0.61; two-sided P < .0001). At the interim OS analysis, the toripalimab arm had a significantly longer OS than the placebo arm (median OS not reached v 17.1 months, hazard ratio = 0.69; 95% CI, 0.53 to 0.92; two-sided P = .0099). The incidence of grade ≥ 3 adverse events was similar between the two arms. Treatment effects were similar regardless of programmed death ligand-1 status. Genomic analysis using whole-exome sequencing from 394 available tumor samples revealed that patients with high tumor mutational burden were associated with significantly better PFS in the toripalimab arm (median PFS 13.1 v 5.5 months, interaction P = .026). Notably, patients with mutations in the focal adhesion-PI3K-Akt signaling pathway achieved significantly better PFS and OS in the toripalimab arm (interaction P values ≤ .001).Toripalimab plus chemotherapy significantly improves PFS and OS in patients with treatment-naive advanced NSCLC while having a manageable safety profile. Subgroup analysis showed the OS benefit was mainly driven by the nonsquamous subpopulation.
Spatial Transcriptomic Analysis of Ovarian Cancer Precursors Reveals Reactivation of IGFBP2 during Pathogenesis
Authors: Yeh Wang, Peng Huang, Brant G. Wang, Tricia Murdock, Leslie Cope, Fang-Chi Hsu, Tian-Li Wang, Ie-Ming Shih
Journal: Cancer Research (2022)

Abstract Elucidating the earliest pathogenic steps in cancer development is fundamental to improving its early detection and prevention. Ovarian high-grade serous carcinoma (HGSC), a highly aggressive cancer, mostly originates from the fallopian tube epithelium through a precursor stage, serous tubal intraepithelial carcinoma (STIC). In this study, we performed spatial transcriptomic analysis to compare STICs, carcinoma, and their matched normal fallopian tube epithelium. Several differentially expressed genes in STICs and carcinomas were involved in cancer metabolism and detected in a larger independent transcriptomic dataset of ovarian HGSCs. Among these, insulin-like growth factor binding protein-2 (IGFBP2) was found to undergo DNA hypomethylation and to be increased at the protein level in STICs. Pyrosequencing revealed an association of IGFBP2 expression with the methylation state of its proximal enhancer, and 5-azacytidine treatment increased IGFBP2 expression. In postmenopausal fallopian tubes, where most STICs are detected, IGFBP2 immunoreactivity was detected in all 38 proliferatively active STICs but was undetectable in morphologically normal tubal epithelia, including those with TP53 mutations. In premenopausal fallopian tubes, IGFBP2 expression was limited to the secretory epithelium at the proliferative phase, and estradiol treatment increased IGFBP2 expression levels. IGFBP2 knockdown suppressed the growth of IGFBP2-expressing tubal epithelial cells via inactivation of the AKT pathway. Taken together, demethylation of the proximal enhancer of IGFBP2 drives tumor development by maintaining the increased IGFBP2 required for proliferation in an otherwise estrogen-deprived, proliferation-quiescent, and postmenopausal tubal microenvironment. Significance: Molecular studies of the earliest precursor lesions of ovarian cancer reveal a role of IGFBP2 in propelling tumor initiation, providing new insights into ovarian cancer development.
<i>Sox17</i> Deficiency Promotes Pulmonary Arterial Hypertension via HGF/c-Met Signaling
Authors: Chan Soon Park, Soo Hyun Kim, Hae Young Yang, Ju-Hee Kim, Ralph Theo Schermuly, Ye Seul Cho, Hyejeong Kang, Jae-Hyeong Park, Eunhyeong Lee, HyeonJin Park, Jee Myung Yang, Tae Wook Noh, Seung-Pyo Lee, Sun Sik Bae, Jinju Han, Young Seok Ju, Jun-Bean Park, Injune Kim
Journal: Circulation Research (2022)

In large-scale genomic studies, Sox17, an endothelial-specific transcription factor, has been suggested as a putative causal gene of pulmonary arterial hypertension (PAH); however, its role and molecular mechanisms remain to be elucidated. We investigated the functional impacts and acting mechanisms of impaired Sox17 (SRY-related HMG-box17) pathway in PAH and explored its potential as a therapeutic target.In adult mice, Sox17 deletion in pulmonary endothelial cells (ECs) induced PAH under hypoxia with high penetrance and severity, but not under normoxia.Key features of PAH, such as hypermuscularization, EC hyperplasia, and inflammation in lung arterioles, right ventricular hypertrophy, and elevated pulmonary arterial pressure, persisted even after long rest in normoxia. Mechanistically, transcriptomic profiling predicted that the combination of Sox17 deficiency and hypoxia activated c-Met signaling in lung ECs. HGF (hepatocyte grow factor), a ligand of c-Met, was upregulated in Sox17-deficient lung ECs. Pharmacologic inhibition of HGF/c-Met signaling attenuated and reversed the features of PAH in both preventive and therapeutic settings. Similar to findings in animal models, Sox17 levels in lung ECs were repressed in 26.7% of PAH patients (4 of 15), while those were robust in all 14 non-PAH controls. HGF levels in pulmonary arterioles were increased in 86.7% of patients with PAH (13 of 15), but none of the controls showed that pattern.The downregulation of Sox17 levels in pulmonary arterioles increases the susceptibility to PAH, particularly when exposed to hypoxia. Our findings suggest the reactive upregulation of HGF/c-Met signaling as a novel druggable target for PAH treatment.
Disruption of the Gut Microbiota Confers Cisplatin Resistance in Epithelial Ovarian Cancer
Authors: Laura M. Chambers, Emily L. Esakov Rhoades, Rashmi Bharti, Chad Braley, Surabhi Tewari, Lexie Trestan, Zahraa Alali, Defne Bayik, Justin D. Lathia, Naseer Sangwan, Peter Bazeley, Amy S. Joehlin-Price, Zeneng Wang, Sumita Dutta, Mohammed Dwidar, Adeline Hajjar, Philip P. Ahern, Jan Claesen, Peter Rose, Roberto Vargas, J. Mark Brown, Chad M. Michener, Ofer Reizes
Journal: Cancer Research (2022)

Abstract Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer death. Despite initial responses to intervention, up to 80% of patient tumors recur and require additional treatment. Retrospective clinical analysis of patients with ovarian cancer indicates antibiotic use during chemotherapy treatment is associated with poor overall survival. Here, we assessed whether antibiotic (ABX) treatment would impact growth of EOC and sensitivity to cisplatin. Immunocompetent or immunocompromised mice were given untreated control or ABX-containing (metronidazole, ampicillin, vancomycin, and neomycin) water prior to intraperitoneal injection with EOC cells, and cisplatin therapy was administered biweekly until endpoint. Tumor-bearing ABX-treated mice exhibited accelerated tumor growth and resistance to cisplatin therapy compared with control treatment. ABX treatment led to reduced apoptosis, increased DNA damage repair, and enhanced angiogenesis in cisplatin-treated tumors, and tumors from ABX-treated mice contained a higher frequency of cisplatin-augmented cancer stem cells than control mice. Stool analysis indicated nonresistant gut microbial species were disrupted by ABX treatment. Cecal transplants of microbiota derived from control-treated mice was sufficient to ameliorate chemoresistance and prolong survival of ABX-treated mice, indicative of a gut-derived tumor suppressor. Metabolomics analyses identified circulating gut-derived metabolites that were altered by ABX treatment and restored by recolonization, providing candidate metabolites that mediate the cross-talk between the gut microbiome and ovarian cancer. Collectively, these findings indicate that an intact microbiome functions as a tumor suppressor in EOC, and perturbation of the gut microbiota with ABX treatment promotes tumor growth and suppresses cisplatin sensitivity. Significance: Restoration of the gut microbiome, which is disrupted following antibiotic treatment, may help overcome platinum resistance in patients with epithelial ovarian cancer. See related commentary by Hawkins and Nephew, p. 4511
Durable response of anaplastic thyroid carcinoma to FS118, a bispecific LAG-3/PD-L1 antibody, after checkpoint inhibitor progression: a case report
Authors: Maxwell J Kroloff, Josefin-Beate Holz, Omer Stern, Christopher J Shepherd, Michelle Morrow, Louis Kayitalire, Deborah J Wong
Journal: Journal for ImmunoTherapy of Cancer (2022)

Anaplastic thyroid cancer represents a rare, highly aggressive form of thyroid cancer with a poor prognosis and an overall survival ranging from 5 to 12 months. Unfortunately, treatment options remain limited, even for patients with a targetable driver mutation. Here, we present a case of a patient with a BRAF V600E-mutated, PD-L1 positive (tumor proportion score of 95%) anaplastic thyroid cancer refractory to standard therapies, including debulking surgery, followed by chemoradiation, who had further progressed on PD-1 monotherapy, and was unable to tolerate BRAF/MEK inhibition. Ongoing treatment with FS118, a bispecific LAG-3/PD-L1 antagonist, has afforded 3 years of disease control, including a late confirmed partial response, with excellent tolerability. Given this response, further investigation is required to delineate the mechanism by which dual PD-L1/LAG-3 blockade by FS118 overcomes initial PD-1 pathway resistance, and therefore, identify which patients are most likely to benefit. Simultaneously, expanded use should be considered for those with refractory disease, especially if PD-L1 positive. Insights Dual PD-L1/LAG-3 blockade may be an effective treatment strategy for refractory metastatic tumors, including anaplastic thyroid cancer.
PPARγ and NOTCH Regulate Regional Identity in the Murine Cardiac Outflow Tract
Authors: Mayyasa Rammah, Magali Théveniau-Ruissy, Rachel Sturny, Francesca Rochais, Robert G. Kelly
Journal: Circulation Research (2022)

The arterial pole of the heart is a hotspot for life-threatening forms of congenital heart defects (CHDs). Development of this cardiac region occurs by addition of Second Heart Field (SHF) progenitor cells to the embryonic outflow tract (OFT) and subsequently the base of the ascending aorta and pulmonary trunk. Understanding the cellular and genetic mechanisms driving arterial pole morphogenesis is essential to provide further insights into the cause of CHDs.
Inhibition of IL-1β release from macrophages targeted with necrosulfonamide-loaded porous nanoparticles
Authors: Bart Boersma, Karin Möller, Lisa Wehl, Viola Puddinu, Arnaud Huard, Sébastien Fauteux-Daniel, Carole Bourquin, Gaby Palmer, Thomas Bein
Journal: Journal of Controlled Release (2022)